A simple method for evaluating abnormal lengthening of the QT interval during the face immersion test.

The slope of the relation between the unadjusted QT interval and heart rate during the face immersion test has been reported to be useful as an index for predicting an abnormal lengthening of the QT interval for children with nonfamilial long QT syndrome. Our goals were to determine whether we can replace the slope of the QT/heart rate relation calculated from all data with that calculated from fewer data and to determine whether we can replace the slope with the corrected QT value by heart rate (QTc value) at the minimum heart rate. We studied 19 children with a prolonged QT interval and 54 control children by using statistical analysis. The slope calculated from the selected data points (at least four) was in agreement with the slope calculated from all data, and the relationship between the slope and the QTc value at the minimum heart rate showed a high correlation. It was determined that we can replace the slope calculated from all data with that calculated from at least four data points and replace the slope with the QTc value at the minimum heart rate as an index for predicting an abnormal lengthening of the QT interval.

Risk factors for persistence of pulmonary arterial branch stenosis in neonates and young infants.

BACKGROUND: Pulmonary arterial branch stenosis (PBS) in neonates is considered to be transient. However, PBS has been found not only in neonates, but also in young infants. Among these patients, we encountered several patients whose PBS was still present after the age of 1 year. METHODS: To clarify the natural history of PBS in neonates and young infants, we retrospectively reviewed the records of 103 patients diagnosed with PBS in the neonatal period and early infancy. RESULTS: The PBS findings were improved in all patients. Pulmonary arterial branch stenosis disappeared in 94 patients by the age of 1 year (group A), but persisted after I year of age in nine patients (group B). Group B patients had a significantly lower mean birth weight and greater deltavelocity (the difference in the peak flow velocity between the main pulmonary artery and stenotic branch) at diagnosis than group A patients. Incidences of low birth weight (< 2,500 g) and deltavelocity above 1.2 m/s were significantly higher in group B than group A patients. There was no significant difference in the frequency of premature infants (gestational age < 36 weeks) between the groups, suggesting that intrauterine growth retardation may be related to developmental abnormalities of the pulmonary arterial branch. CONCLUSIONS: All cases of PBS in neonates and young infants were improved. However, PBS persisted in some patients after the age of 1 year. Low birth weight and deltavelocity above 1.2 m/s are risk factors for persistent PBS. Pulmonary arterial branch stenosis was not present after the age of 1 year in 62 of 63 patients without either of these risk factors.

Bilateral coronary artery dilatation in a child with Noonan syndrome.

A rare case of a child with Noonan syndrome who had huge bilateral coronary artery dilatation is presented. Noonan syndrome is one of the most common nonchromosomal syndromes seen in children with cardiovascular abnormalities. Coronary artery abnormality should be considered in Noonan syndrome, because this syndrome may be associated with a higher incidence of coronary anomalies than previously thought.

Face immersion in cold water induces prolongation of the QT interval and T-wave changes in children with nonfamilial long QT syndrome.

We investigated the relation between heart rate and the QT interval using face immersion in cold water in children with long QT syndrome (LQTS) without a family history of this condition, and in control children. The face immersion test revealed that all children with high probability of LQTS had a significantly longer QT interval than control children during face immersion, and that the test could induce T-wave alternans or a notched T-wave in all children with a high probability of LQTS.

Primary mouse keratinocyte cultures contain hair follicle progenitor cells with multiple differentiation potential.

The interfollicular epidermis contains a single type of terminally differentiated keratinocytes, whereas hair follicles are composed of a minimum of six or seven distinct types. Whether or not these various populations of terminally differentiated keratinocytes originate from one or more progenitor cells has not been established. A related and important question is whether keratinocyte progenitor cells with a pluripotent potential, able to form not only epidermis but also hair follicles, can be maintained in vitro for any period of time. We have addressed these questions using skin reconstitution assays with admixed populations of genetically labeled, cultured keratinocytes. Examination of reconstituted epidermis and hair follicles showed that neither was composed of a random mixture of differently labeled keratinocytes, as would be predicted if they originated from a random reassociation of cells. Instead, the reconstituted interfollicular epidermis contained distinct columnar units, comprising all the overlying layers and most likely derived from a single progenitor cell. In contrast, hair follicles were found to be composed of cells of multiple origin, with each population showing a striking localization to a separate concentric region. The vast majority of reconstituted follicles appeared to derive from a minimum of two or, in a significant fraction of cases, three progenitor cells, one for the generation of the shaft (cuticle, cortex, and medulla), one for the inner root sheath, and the third for the outer root sheath. The general implications of these findings for epidermis and hair follicle formation and for keratinocyte stem cell cultivation are discussed.

The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation.

Mutations in the winged-helix nude (whn) gene result in the nude mouse and rat phenotypes. The pleiotropic nude phenotype which affects the hair, skin, and thymus suggests that whn plays a pivotal role in the development and/or maintenance of these organs. However, little is known about whn function in these organs. We show here that in skin whn is specifically expressed in epithelial cells and not the mesenchymal cells, and using a hair reconstitution assay, we demonstrate that the abnormal nude mouse hair development is attributable to a functional defect of the epithelial cells. Examination of nude mouse primary keratinocytes in culture revealed that these cells have an increased propensity to differentiate in an abnormal fashion, even under conditions that promote proliferation. Furthermore, nude mouse keratinocytes displayed a 100-fold increased sensitivity to the growth-inhibitory/differentiation effects of the phorbol ester TPA. In parallel with these findings, we directly show that whn functions as a transcription factor that can specifically suppress expression of differentiation/TPA-responsive genes. The region of Whn responsible for these effects was mapped to the carboxy-terminal transactivating domain. These results establish whn as a key regulatory factor involved in maintaining the balance between keratinocyte growth and differentiation. The general implications of these findings for an epithelial self-renewal model will be discussed.

Anti-IL-1 alpha autoantibodies in patients with rheumatic diseases and in healthy subjects.

We have developed a quantitative assay for IgG autoantibodies against IL-1 alpha using protein A-Sepharose CL-4B. We examined the autoantibodies in sera from 107 healthy subjects, 151 patients with rheumatoid arthritis (RA), 64 patients with systemic lupus erythematosus (SLE) and 16 patients with systemic sclerosis. The frequency of positive sera for the autoantibodies in patients with RA was 16.6%, which was about three times more frequent (P less than 0.01) than that in healthy subjects (5.6%) or that in patients with SLE (4.7%). Only one serum of 16 patients with systemic sclerosis was positive for the autoantibodies. Neutralizing activity of the autoantibodies was demonstrated by murine thymocyte proliferation assay. The concentrations of IgG at 50% inhibition of IL-1 alpha (15 pM) induced thymocyte proliferation ranged between 0.1 and 0.5 mg/ml. A time-course study showed fluctuations of the titres of the autoantibodies in parallel with the disease activity of RA. These results suggest that the anti-IL-1 alpha autoantibodies present in the sera and possibly some other body fluids may be involved in the regulation of IL-1 activity in vivo.

Demonstration of neutralizing autoantibodies against IL-1 alpha in sera from patients with rheumatoid arthritis.

We have recently reported the presence of IgG which has a potent inhibitory activity against IL-1 alpha in some sera from patients with rheumatoid arthritis. The mechanism of this inhibition by IgG against IL-1 alpha is now elucidated. IgG with IL-1 alpha-inhibitory activity inhibited the binding of 125I-IL-1 alpha to receptors on rheumatoid synovial cells. In addition, preincubation of synovial cells with the inhibitory IgG did not block the binding of 125I-IL-1 alpha to receptors, suggesting a direct interaction between IgG and IL-1 alpha. To examine which region of the IgG, namely Fab or Fc region, has the inhibitory activity, the IgG was digested with papain, and Fab and Fc fragments were purified. Fab fragments, but not Fc fragments, inhibited both IL-1 alpha-induced thymocyte-proliferation and the binding of 125I-IL-1 alpha to receptors. We further demonstrated that the inhibitory IgG which was bound to protein A Sepharose could bind a significant amount of 125I-IL-1 alpha, whereas only a negligible binding of the radiolabeled ligand was detected when IgG without the inhibitory activity was used as control. Moreover, the binding of 125I-IL-1 alpha to IgG with the inhibitory activity was clearly blocked by Fab fragments of IgG having the inhibitory activity. Finally, affinity-purified IgG over an IL-alpha affinity column showed approximately 100-fold more potent inhibitory activity on IL-1 alpha-induced thymocyte proliferation compared with untreated IgG. From these results, we conclude that IgG molecules with IL-1-alpha-inhibitory activity are neutralizing autoantibodies against IL-1 alpha.

Optical phase fluctuations thermally induced in a single-mode optical fiber.

Mathematical expressions have been derived on fluctuations of optical phase and frequency of a light wave which are thermally caused in a single-mode optical fiber in terms of fiber length, thermal coherence length, and fluctuation frequency. Fluctuations of optical phase and temperature were measured at a wavelength of 0.6328 microm by Mach-Zehnder interferometry, and the results are compared with theoretical predictions. A minimum detectable temperature change through optical phase shift depends on frequency stability of a source laser. It is 10(-5) K with a fractional frequency fluctuation of 10(-9).

Preliminary experiment for optical heterodyne communication with a single-mode optical fiber by using frequency-stabilized He-Ne lasers.

Frequency fluctuation in a single-mode optical fiber is briefly discussed, and a preliminary experiment for optical heterodyne communication in a single-mode fiber is carried out with the aid of frequency-stabilized He-Ne lasers operating at a wavelength of 0.633 microm. As a result, we have obtained clear demodulated signals, having sinusoidal, triangular, and rectangular waveforms, through an optical fiber 100 m in length.